SUPPLEMENTARY INFORMATION:

I. Background

FDA is announcing the availability of a draft guidance for industry and FDA staff entitled “Postmarket Safety Reporting for Combination Products.” This guidance addresses how to comply with the final rule on postmarketing safety reporting (PMSR) requirements for combination products that FDA issued on December 20, 2016 (81 FR 92603, hereafter referred to as the “combination product PMSR final rule”). Combination products are products composed of two or more different types of medical products (drug, device, and/or biological product). Although the PMSR regulations for drugs, devices, and biological products share many similarities, each set of regulations establishes distinct reporting requirements, standards, and timeframes. The final rule provides clarity on the PMSR requirements for combination products to ensure consistent and complete reporting while avoiding duplication.

Elsewhere in this issue of the Federal Register , FDA is also publishing a compliance policy guidance for the combination product PMSR final rule.

The combination product PMSR final rule applies to combination products that are subject to premarket review by FDA. The entities subject to the final rule are “Combination Product Applicants” and “Constituent Part Applicants.” A Combination Product Applicant holds the only application for a combination product or all the applications for the separately marketed constituent parts of a combination product. A Constituent Part Applicant holds an application for a constituent part of a combination product the constituent parts of which are marketed under separate applications held by different applicants. Major provisions of the final rule are discussed in the guidance including:

• Application Type-Based PMSR. These requirements apply to both Combination Product Applicants and Constituent Part Applicants and are based on the application type under which the combination product or constituent part received marketing authorization.
• Constituent Part-Based PMSR. These requirements apply only to Combination Product Applicants and are based on the types of constituent parts included in the combination product. The rule provides mechanisms for Combination Product Applicants to submit a single report to satisfy multiple reporting requirements if all of the information to be reported can be submitted in the same manner and the report satisfies all applicable reporting requirements, including all submission timelines.
• Information Sharing. These requirements apply only to Constituent Part Applicants, mandating that these applicants share certain adverse event information with one another relating to their combination product.
• Submission Process for Combination Product PMSR Information. These requirements specify how Combination Product and Constituent Part Applicants must submit PMSR information to the Agency.
• Records Retention. These requirements specify what records Combination Product and Constituent Part Applicants must maintain and how long to maintain them.

II. Other Issues for Consideration

The combination product PMSR final rule allows FDA to receive complete, timely postmarketing safety information regarding combination products, which is necessary to assure the continued safety and effectiveness of such products, while minimizing unnecessary duplication and burdens on Combination Product Applicants and Constituent Part Applicants. In developing this guidance document to accompany the final rule, FDA has clarified ways in which Combination Product Applicants can streamline PMSR (see section V.A.3 of the guidance). The guidance clarifies under what circumstances the criteria for being able to submit a single report to FDA are met, i.e., that: (1) The reports can be submitted in the same manner and (2) the combined report satisfies all applicable reporting requirements, including submission timelines (see section IV.C of the guidance). FDA encourages comments on guidance content and mechanisms to improve reporting efficiency while still ensuring complete and timely reporting or topics where additional detailed discussion may be helpful in the guidance. In particular, FDA requests feedback on the following issues for consideration to assist the Agency in determining whether additional streamlining of reports may be appropriate:

1. There may be events that would be reportable for a Combination Product Applicant as a malfunction and/or a Field Alert Report (FAR) and/or a Biological Product Deviation Report (BPDR), e.g., a drug-device combination product that failed to meet specifications may trigger both a malfunction report and FAR. FDA requests feedback on circumstances under which such reporting may be redundant or otherwise unnecessary and, if so, alternative reporting approaches that will assure timely and complete reporting of information to FDA. FDA encourages the use of example scenarios to illustrate circumstances under which submitting one or a subset of such reports may be sufficient to ensure timely and complete reporting.

2. Although outside the scope of the combination product PMSR final rule, in response to comments to the combination product PMSR proposed rule, FDA has addressed certain reporting considerations for entities involved with the manufacture and distribution of combination products but that are not “applicants” subject to this rule (see Appendix 3 of the guidance). FDA requests feedback on what, if any, additional guidance would be helpful to such entities.

3. FDA is considering updating the Vaccine Adverse Event Reporting System (VAERS) with data elements similar to those described in section V.B.2 and Appendix 4 of the guidance for the FDA Adverse Events Reporting System (FAERS) and the Electronic Medical Device Reporting (eMDR) system. FDA is also evaluating what additional data elements to include in VAERS with respect to combination products and welcomes comments from combination product vaccine reporters on this topic.

4. FDA also received comments to the combination product PMSR proposed rule related to the safety reporting requirements for investigational combination products. Although investigational combination products are outside the scope of the combination product PMSR final rule and this guidance, we will consider comments from sponsors on the challenges and the need for additional transparency related to safety reporting for investigational combination products. FDA will consider these comments in determining the need for additional policy and guidance on this topic.

III. Significance of Guidance

This draft guidance is being issued consistent with FDA's good guidance practices regulation (21 CFR 10.115). The draft guidance, when finalized, will represent the current thinking of FDA ( printed page 12294) on “Postmarket Safety Reporting for Combination Products.” It does not establish any rights for any person and is not binding on FDA or the public. You can use an alternative approach if it satisfies the requirements of the applicable statutes and regulations. This guidance is not subject to Executive Order 12866.

IV. Paperwork Reduction Act of 1995

This guidance refers to previously approved collections of information found in FDA regulations. These collections of information are subject to review by the Office of Management and Budget (OMB) under the Paperwork Reduction Act of 1995 (44 U.S.C. 3501-3520). The collections of information in 21 CFR 314.80(c) and (e), as well as for 21 CFR 314.81(b) are approved under OMB control numbers 0910-0001, 0910-0230, and 0910-0291. The information collection provisions for 21 CFR 600.80 and 600.81 are approved under OMB control number 0910-0308. Those for 21 CFR 606.170 are approved under OMB control number 0910-0116. Those for 21 CFR 606.171 are approved under OMB control number 0910-0458. The information collection provisions for 21 CFR 803.50, 803.53, and 803.56 are approved under OMB control numbers 0910-0291 and 0910-0437. The information collection provisions for 21 CFR 806.10 and 806.20 are approved under OMB control number 0910-0359. The information collection provisions for 21 CFR 4.102, 4.103, and 4.105 are approved under OMB control number 0910-0834.

V. Electronic Access

Persons with access to the internet may obtain the draft guidance at either https://www.fda.gov/​CombinationProducts/​GuidanceRegulatoryInformation/​ucm109110.htm or https://www.regulations.gov.